The present proposal emphasizes new and existing areas of clinical research and is designed to provide an integrated approach to clinical investigation. Over 70 faculty members from the Schools of Medicine, Dentistry, Pharmacy and Nursing will participate in the planned clinical investigations which include the following studies. Research in endocrinology will define the role of corticotropin-releasing factor in the diagnosis of Cushing's disease and localization of pituitary adenomas as well as the long-term effects on hormonal secretion of transsphenoidal surgery for children with Cushing's disease. The evaluation of the therapeutic benefits of new analogs of LRF (agonists) on pituitary hormonal secretion and attainment of normal final height as well as the resumption of normal pubertal development will be continued. The effect of IGF-I on protein synthesis and turnover in patients with growth hormone deficiency will be studied. Immune mechanisms accounting for the induction of tolerance following haploidentical bone marrow transplantation for children with stem cell deficiencies or malignancies will be investigated. The ability to achieve stem cell engraftment following bone marrow transplant in utero will be studied. Research in pediatric AIDS will focus on new approaches to early diagnosis, identification of early changes in immune function investigation of early neurodevelopmental consequences, and early provision of innovative therapy. Chromogranin A (a serum marker of tumor cell lysis) in neuroblastoma as well as innovative treatment of this disorder with 131-I-MIBG will be explored. Mechanisms and efficacy of new therapies for organic acidemias will be evaluated. The pathogenesis of neurologic sequelae in patients with galactosemia, Menkes syndrome and central nervous system systemic lupus erythematosis will be investigated utilizing magnetic resonance spectroscopy. The natural history of human papilloma virus in teens will be defined. The acquisition of the Neonatal PCRC Unit will allow investigators to study the impact of recombinant human erythropoietin on the anemia of prematurity, abnormalities of the neonatal immune response to herpes simplex infection, the neurological complications in infants of cocaine-using mothers, and the pathogenesis of decreased chronic lung disease in preterm infants treated antenatally with thyrotropin-releasing factor and corticosteroid. With the expansion of the existing outpatient facility, additional outpatient protocols can be accommodated to enhance the productivity of the center.